On September 21, 2022, the Food and Drug Administration granted accelerated approval to selpercatinib (Retevmo, Eli Lilly and Company) for adult patients with locally advanced or metastatic solid tumors with a rearranged during transfection (RET) gene fusion that have progressed on or following prior systemic treatment or who have no satisfactory alternative treatment options.
Efficacy was demonstrated in LIBRETTO-001 (NCT03157128), a multicenter, open-label, multi-cohort trial that evaluated 41 patients with RET fusion-positive tumors (other than non-small cell lung cancer and thyroid cancer) with disease progression on or following prior systemic treatment or who had no satisfactory alternative treatment options. The efficacy evaluation was supported by data in 343 patients with RET fusion-positive NSCLC and thyroid cancer enrolled in the same trial already described in product labeling. Patients received selpercatinib until disease progression or unacceptable toxicity.
The primary efficacy measures were overall response rate (ORR) and duration of response (DOR) as determined by a Blinded Independent Review Committee (BIRC). Among 41 evaluable patients, ORR was 44% (95% CI: 28, 60) with a DOR of 24.5 months (95% CI: 9.2, not estimable). Tumor types with responses included pancreatic adenocarcinoma, colorectal, salivary, unknown primary, breast, soft tissue sarcoma, bronchial carcinoid, ovarian, small intestine, and cholangiocarcinoma.
The median age of patients was 50 years (range 21 to 85). Selected demographics were as follows: 54% female; 68% White, 24% Asian, 4.9% Black; 7% Hispanic/Latino; 95% had ECOG performance status of 0 or 1; 95% had metastatic disease. Thirty-seven patients (90%) received prior systemic therapy (median 2 [range 0-9]; 32% received 3 or more). The most common cancers were pancreatic (27%), colorectal (24%), salivary (10%), and unknown primary (7%). RET fusion-positive status was detected in 97.6% of patients using NGS and 2.4% using FISH.
The most common adverse reactions (≥25%) in patients were edema, diarrhea, fatigue, dry mouth, hypertension, abdominal pain, constipation, rash, nausea, and headache.
The recommended selpercatinib dose based on body weight is:
- Less than 50 kg: 120 mg orally twice daily
- 50 kg or greater: 160 mg orally twice daily
This review used the Assessment Aid, a voluntary submission from the applicant to facilitate the FDA’s assessment. The FDA approved this application 2 months ahead of the FDA goal date.
This application was granted accelerated approval based on overall response rate and duration of response. Continued approval may be contingent upon verification of clinical benefit in confirmatory trials.
This application was granted priority review. A description of FDA expedited programs is in the Guidance for Industry: Expedited Programs for Serious Conditions-Drugs and Biologics. The application also was granted orphan drug designation.
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